Mye-EUNITER
 

Weiss, Günter

The scientific focus of our laboratory is dedicated to investigations regarding the role of innate immune cells with a focus on macrophages but recently also on neutrophils. We have been working with macrophages for almost 25 years focusing on the function of innate resistance genes in macrophages and neutrophils and their role for the control of infections and inflammatory diseases . In addition we studied metabolic alterations within macrophages in the course of infections (e.g. modulation of iron homeostasis) and how manipulation of such metabolic traits affect host responses and/or the pathogenicity and proliferation of microbes within macrophages.

Models/disease studied:

We have further expertise in the use of different infectious disease models in vitro and in vivo, mainly using pathogens which specifically target macrophage and we have employed disease models with inducible or permanent knock out of macrophage genes with importance in host-pathogen interaction

Cellular models: human and murine macrophage cell lines; primary monocytes from patients with infectious disease and/or disturbances of iron homeostasis
macrophages with shRNA inducible knock down of iron metabolism and hypoxia genes, macrophage overexpressing Nramp1r and s variants; inducible knock down of genes in macrophages by siRNA and Crips technology
mouse models: mice with knock out of iron metabolism (Hfe, H-ferritin, lipocalin-2) or innate resistance genes genes (iNOS, Lcn2, IL-10); macrophage specific gene knock (LysMCre technolgy)
infectious disease models: pathogens used in vitro and in vivo: Salmonella typhi murium, Chlamydia pneumoniae, Listeria monocytogenes, Escherichia coli, Staphylococcus aureus (and mutanted bacterial strains)
non infectious inflammation models: PGS-AG -rats, zymosan mice.

Major cell types studied & key scientific question(s)

Macrophages: systemic analysis of mechanistic aspects of iron homeostasis in macrophages upon infection with intracellular and extracellular pathogens;
Importance of tissue specific macrophage localization and plasticity for immune control of infection and metabolic (nutritional) immunity
characterization of gene expression, proteomic and metabolic profile of macrophages involved either in inflammation/infection driven alterations of iron homeostasis, erythrophagocytosis and containment/elimination of pathogens;
characterization of macrophages protein expression by FACS technology in vivo (mice and human) and linking specific expression pattern to disease outcome in patients with sepsis (development of bioassays)

Technology used:

Cell and in vivo models of infectious diseases employing specific genetic deletions of macrophage and iron metabolism genes along with bacterial strains bearing mutations in pathogenicity or iron metabolism genes
In vivo imaging of infections using fluorescence labeled bacteria
FACS mediated sorting of macrophages loaded with/without bacteria and their subsequent analysis
FACS mediated functional characterisation and sorting of myeloid cells
inducible and genetic knock down of genes of interest
characterisation of tissue and cell specific gene expression pattern of myeloid cells by RT-PCR, Western blotting
functional chatracterisation of myeloid cells in regards to chemotaxis, bacterial containment and elimination
clodoronate inducible macrophage deletion
bone marrow transplantation in mice (adaptive transfer of cells)

Selected publications relevant to Mye-EUNITER

  1. Nairz M, Schleicher U, Schroll A, Sonnweber T, Theurl I, Ludwiczek S, Talasz H, Brandacher G Moser PL, Muckenthaler MU, Fang FC, Bogdan C, Weiss G. Nitric oxide-mediated regulation of ferroportin-1 controls macrophage iron homeostasis and immune function in Salmonella infection, J Exp Med , 210; 855-873, 2013.
  2. Nairz M, Schroll A, Moschen AR, Sonnweber T, Theurl M, Theurl I, Taub N, Jamnig C, Neurauter D, Huber LA, Tilg H, Moser PL, Weiss G. Erythropoietin contrastingly affects bacterial infection and experimental colitis by inhibiting NF-κB-inducible immune pathways. Immunity 34: 61-74. 2011 
  3. Tancevski I, Nairz M, Duwensee K, Auer K, Schroll A, Heim C, Feistritzer C,
    Hoefer J, Gerner RR, Moschen AR, Heller I, Pallweber P, Li X, Theurl M,
    Demetz E, Wolf AM, Wolf D, Eller P, Ritsch A, Weiss G. Fibrates ameliorate
    the course of bacterial sepsis by promoting neutrophil rectruitment via CXCR2.
    EMBO Mol Med. 6:810-20. 2014
  4. Ludwiczek S., Theurl I, Muckenthaler M.U., Jakab M., Mair S M., Theurl M., Kiss J., Paulmichl M., Hentze M.W., Ritter M., Weiss G. Ca2+ channel blockers reverse iron overload by a novel mechanism via divalent metal transporter-1. Nat Med 13:448-454, 2007
  5. Nairz M, Theurl I, Schroll A, Theurl M, Fritsche G, Lindner E, Seifert M, Crouch M-L, Hantke K, Akira S, Fang FC, Weiss G. Absence of functional Hfe protects mice from invasive Salmonella enterica serovar Typhimurium infection via induction of lipocalin-2. Blood 114:3642-51, 2009 

Contact details:

Department of Internal Medicine VI (Infectious Diseases, Immunology, Rheumatology, Pneumology)
Innsbruck Medical University
Anichstrasse 35
A-6020 Innsbruck
Austria

Tel: 0043/512/504/23251

guenter.weiss@i-med.ac.at